Role for proteasome activator PA200 and postglutamyl proteasome activity in genomic stability Academic Article uri icon

Overview

MeSH Major

  • Genomic Instability
  • Nuclear Proteins
  • Proteasome Endopeptidase Complex

abstract

  • Proteasome activator PA200 enhances proteasome-mediated cleavage after acidic residues in vitro; however, its role within cells is not known. Here, we show that, in response to ionizing radiation, PA200 forms hybrid proteasomes with 19S caps and 20S core proteasomes that accumulate on chromatin, leading to an increase in proteolytic activity. Unlike many other proteins that respond to DNA damage, the response of PA200 appears to be independent of Ataxia Telangiectasia Mutated and p53, but dependent on DNA-dependent protein kinase activity. Nonetheless, PA200 is critical because PA200-knockdown cells show genomic instability and reduced survival after exposure to ionizing radiation. This phenotype is reproduced by specific inhibition of postglutamyl activity of proteasomes, but combined treatment with PA200 siRNA and postglutamyl inhibitor does not show additive effects on survival. Together, these data suggest a unique role for PA200 in genomic stability that is likely mediated through its ability to enhance postglutamyl cleavage by proteasomes.

publication date

  • October 21, 2008

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC2570974

Digital Object Identifier (DOI)

  • 10.1073/pnas.0803145105

PubMed ID

  • 18845680

Additional Document Info

start page

  • 16165

end page

  • 70

volume

  • 105

number

  • 42